Benzimidazole derivatives, i.e. 2-(2-pyridylmethylsulfinyl)benzimidazole derivatives which are of value as a medicine such as anti-ulcer agent, have been known in European Patent Application Publication No. 302720 (Japanese Patent Application Laid-open No. 1-131176), European Patent Application Publication No. 5129 (Japanese Patent Application Laid-open No. 58-192880), Japanese Patent Application Laid-open No. 61-22079, Japanese Patent Application Laid-open No. 64-6270, U.S. Pat. No. 4,255,431, European Patent Applicati,on Publication Nos. 45200, 74341, 80602, 174726, 175464, British Patent Application Publication No. 2134523.
European Application Publication No. 302720 (Japanese Patent Application Laid-open No. 1-131176) describes in Example 1 that 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-benzimi dazole was obtained as white crystals by subjecting a solution of 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylthio]benzimidazol e (monohydrate) in dichloromethane to an oxidation reaction with hydrogen peroxide using vanadium pentoxide as a catalyst, concentrating the reaction mixture, adding ethanol-water (9:1) to the residue, recovering the resulting crystals by filtration, rinsing them, dissolving this crystal crop in ethanol-water (9:1) at an elevated temperature (65-70.degree. C.), filtering the solution when hot, cooling the filtrate with ice, recovering the resulting crystals by filtration, rinsing them, and drying them in vacuo.
Any compound in the 2-(2-pyridylmethylsulfinyl)-benzimidazole derivatives tends to lose stability and undergo decomposition when it contains traces of a solvent, particularly water, in its crystal structure and, therefore, this residual solvent in the crystal must be reduced to a minimum.
However, when the production procedure for 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-methylsulfinyl]benzimi dazole as described in said EP-302720 is followed, water and ethanol can hardly be eliminated from the product and the resulting crystals inevitably contain fair amounts of water and ethanol. Thus, the benzimidazole compound provided by the process described in the above literature is a solvate containing one molecule each of water and ethanol and it is very difficult to desolvate the compound by vacuum drying without detracting from the stability of the product.
There is a serious problem with the above benzimidazole compound in the form of a solvate, particularly a hydrate, for being heat-labile, it is easily decomposed in the vacuum drying step, particularly under heating, thus depressing the purity of the product benzimidazole compound. Therefore, there has been an outstanding demand for a supply of solvent-free crystals of said benzimidazole compound and development of a high-production-scale, highly workable, and effective desolvation technology for providing such crystals.